The laboratory has actively investigated the molecular mechanisms of action of several human cytokines including, IL 2, IL 3, and GM-CSF. IL 2 and other hematopoietic cytokines were shown to regulate tyrosine phosphorylation in situ. Although the receptors for these cytokines do not contain intrinsic kinase domains, the data suggested that they are in a tight association with one or more tyrosine kinases. We have developed specialized methods to isolate in vitro the tertiary structure of the IL 2 receptor subunits and the kinase responsible for the transmembrane signal. These methods will allow the biochemical purification and subsequent molecular cloning of this receptor specific protein kinase. Additionally, we have molecularly cloned five new human tyrosine kinases from human leukemic cell mRNA which may be overexpressed in some human leukemic cell Types. We will continue to characterize these genes and their potential role in leukemogenesis. The laboratory has identified a transcriptional regulatory element found within the promoter regions of the IL 2R alpha gene and the homologous element in the Human Immunodeficiency Virus-1 long terminal repeat. This protein was purified, and found to be under the control of a cytoplasmic inhibitor. The activation of this protein in situ was inhibited by cyclosporin A.